It is proposed that control of lipid metabolism in heart and adipose tissue from models of diabetes/obesity and normal rodents will be investigated. In the in vivo situation, it is difficult or even impossible to sort out the control factors involved in a metabolic pathway. By the use of the isolated fat cell and perfused heart technique, one is able to control these factors to a high degree by altering the substrate(s) concentration and/or by the addition of hormones at varying concentrations. Initially, the factors influencing heart triglyceride breakdown will be investigated in isolated fat cells and perfused hearts from normal rats and mice. Then, experiments will be carried out to investigate if control mechanisms of triglyceride breakdown are similar and/or abnormal in isolated fat cells and perfused hearts obtained from the rodent models of diabetes/obesity. The long term goal of our work is to evaluate the relative contribution of hyperinsulinemia, insulin resistance, hyperglycemia and ketoacidosis in these models to the metabolic aberrations present in heart and adipose tissue which possess many, if not all, of the characteristics of the various syndromes of human diabetes and/or obesity. BIBLIOGRAPHIC REFERENCES: Hron, W. T., Jesmok, G. J., Lombardo, Y. B., Menahan, L. A. and Lech, J. J.: Dependency of hormone stimulation of glycerol release on perfusate (Ca ions) in the isolated perfused rat heart. J. Mol. Cell. Cardiology. (In Press) 1977. Jesmok, G. J., Calvert, D. N. and Lech, J. J.: The effect of inotropic agents on glycerol release in the isolated perfused rat heart. J. Pharm. Exp. Ther. (In Press) 1977.